This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Despite gains in the reduction of tobacco use in adults, cigarette smoking is a primary contributor to many of the leading causes of death in the United States;heart disease, lung cancer, and chronic obstructive pulmonary disease (COPD). Tobacco smoking is the primary risk factor for the development of COPD,1, 2 an insidious, often progressive, and generally irreversible form of lung destruction.3 The incidence and mortality rates for COPD are higher among Caucasians than African Americans.4 This observation may be partly explained by historical trends in cigarette smoking. African Americans initiate smoking at later ages than Caucasians,5 smoke fewer cigarettes per day5 and develop COPD at younger ages and with lower total tobacco smoke exposure.6,7 In addition, African American males have higher lung cancer incidence and mortality.8-11 It is well known that African Americans have higher serum cotinine levels per cigarette smoked, slower clearance of cotinine, higher intake of nicotine per cigarette smoked12 and exhibit more loss of lung function per cigarette smoked.13 Metabolites of nicotine, 4-(Methylnitrosamino)-1-(3-pyridyl)-1butanol (NNAL) and its glucuronides are measurable in the urine. NNAL has been shown to be related to risk for developing lung cancer.14 NNAL was reported to be higher in a small study of African American male smokers vs. Caucasian male smokers5 but its relationship to COPD has not been demonstrated. Societal, environmental, and genetic risk factors likely contribute to these observed health disparities. African Americans are unique in that they have varying proportions of European, Native American, and African continental genetic ancestry. We hypothesize that among African Americans, the distribution of these risk factors varies by ancestry. Specifically, we hypothesize that genetic ancestry co-varies with NNAL levels and therefore risk of developing COPD. For this pilot proposal, we will recruit African American smokers with and without COPD and measure NNAL levels. We will determine if higher African ancestry is associated with increased levels of NNAL and COPD. To test this hypothesis, we propose the following specific AIMS: Specific Aim 1. We will enroll a cohort of 200 African Americans smokers with and without COPD, utilizing a database of study subjects locally recruited into an ongoing study of the genetics of COPD susceptibility. Specific Aim 2. We will measure urinary cotinine and urinary NNAL (total, NNAL-gluc, NNAL-gluc/NNAL) in the cohort of subjects described in Specific Aim 1 for association with COPD. Specific Aim 3. We will obtain and biologically bank whole blood specimens from the subjects enrolled in Specific Aim 1 for future DNA testing and admixture analyses. We will perform a biochemical investigation of urinary levels of tobacco-specific nitrosamine metabolites in African American smokers with and without COPD.